A multiple Piccolino-RIBEYE interaction supports plate-shaped synaptic ribbons in retinal neurons

Item Type:	Article
Title:	A multiple Piccolino-RIBEYE interaction supports plate-shaped synaptic ribbons in retinal neurons
Creators Name:	Müller, T.M. and Gierke, K. and Joachimsthaler, A. and Sticht, H. and Izsvák, Z. and Hamra, F.K. and Fejtová, A. and Ackermann, F. and Garner, C.C. and Kremers, J. and Brandstätter, J.H. and Regus-Leidig, H.
Abstract:	Active zones at chemical synapses are highly specialized sites for the regulated release of neurotransmitters. Despite a high degree of active zone protein conservation in vertebrates, every type of chemical synapse expresses a given set of protein isoforms and splice variants adapted to the demands on neurotransmitter release. So far, we know little about how specific active zone proteins contribute to the structural and functional diversity of active zones. In this study, we explored the nano-domain organization of ribbon-type active zones by addressing the significance of Piccolino, the ribbon synapse specific splice variant of Piccolo, for shaping the ribbon structure. We followed up on previous results, which indicated that rod photoreceptor synaptic ribbons lose their structural integrity in a knockdown of Piccolino. Here, we demonstrate an interaction between Piccolino and the major ribbon component RIBEYE that supports plate-shaped synaptic ribbons in retinal neurons. In a detailed ultrastructural analysis of three different types of retinal ribbon synapses in Piccolo/Piccolino deficient male and female rats, we show that the absence of Piccolino destabilizes the superstructure of plate-shaped synaptic ribbons, although with variable manifestation in the cell types examined. Our analysis illustrates how the expression of a specific active zone protein splice variant, like Piccolino, contributes to structural diversity of vertebrate active zones. SIGNIFICANCE STATEMENT: Retinal ribbon synapses are a specialized type of chemical synapse adapted for the regulated fast and tonic release of neurotransmitter. The hallmark of retinal ribbon synapses is the plate-shaped synaptic ribbon, which extends from the release site into the terminals' cytoplasm and tethers hundreds of synaptic vesicles. Here, we show that Piccolino, the synaptic ribbon specific splice variant of Piccolo, interacts with RIBEYE, the main component of synaptic ribbons. This interaction occurs via several PxDLS-like motifs located at the C-terminus of Piccolino, which can connect multiple RIBEYE molecules. Loss of Piccolino disrupts the characteristic plate-shaped structure of synaptic ribbons indicating a role of Piccolino in synaptic ribbon assembly.
Keywords:	Ribbon Synapse, Photoreceptor, Active Zone, Piccolino, RIBEYE, Animals, Mice, Rats
Source:	Journal of Neuroscience
ISSN:	0270-6474
Publisher:	Society for Neuroscience
Volume:	39
Number:	14
Page Range:	2606-2619
Date:	3 April 2019
Official Publication:	https://doi.org/10.1523/JNEUROSCI.2038-18.2019
External Fulltext:	View full text on PubMed Central
PubMed:	View item in PubMed

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